Advances in Life Sciences, particularly in genomics and proteomics, have greatly increased the potential number of reactions and analyses that must be performed by the biotechnology and pharmaceutical industries. An estimated 30 million tests are required to screen a typical pharmaceutical company's compound library against target receptors. The typical number of tests will increase dramatically as information is gleaned from the sequencing of the human genome. To meet these increasing throughput demands in an economically feasible manner, miniaturization of tests is imperative.
Technological advances are enabling the demonstration and use of microscale chemical/biochemical reactions for performing various types of analyses. Implementation of these reactions at such smaller scales offer economies that are unmatched by conventional approaches. Reduced volumes can lower costs by an order of magnitude but conventional liquid-handling devices fail at the required volumes. Parallel implementation provides even greater advantages as demonstrated by the use of high-density plates for screening and high-density MALDI-TOF plates for mass spectrometry analyses of proteins. The rate-limiting hardware is low volume liquid transfer technology that is robust and scalable for compounds of interest. With growing demand, the development of liquid handling devices adept at manipulating sub-microliter volumes (i.e., nanoliters to microliters) of multiple reagent is needed.
Most current systems for handling liquid reagents often employ a “pick and place” technique where a sample from a source plate, usually a microtiter plate, is picked up and placed into another reservoir known as the target plate. This technique is often applied for replicating plates, where scale reduction between the source and the target plates are beneficially realized. Typically, an appropriate volume is aspirated from a source plate and deposited to a target site on a multiple target plate. In this arrangement, reduced sample volumes and sample spacing are required for higher degrees of miniaturization.
However, many of these older conventional automated liquid handling systems currently in use for nucleic acid sequencing or other molecular biology procedures for therapeutic and research procedures such as DNA restriction mapping, DNA probe generation, DNA replication, DNA sample processing and cycle sequencing are designed to manipulate and dispense fluids in the microliters to milliliters range.
While these conventional liquid handling workstations are adequate for manipulating larger volume fluid dispensing for the particular applications which they address (e.g., about 1 μl to about 10 ml), they are not suitable for accurately delivering sub-microliter volume fluids (i.e., nanoliter to microliter) to perform the above-mentioned applications. Thus, it would be desirable to provide a secondary liquid dispensing system and method that cooperates with an existing, conventional primary liquid handling device to enable nanoliter to microliter dispensing of fluids, while maintaining the microliters to milliliters fluid dispensing of the primary liquid dispensing system